Inflammation is an underlying risk factor for aging-related physical disability; therefore, interventions that reduce inflammation in the elderly may be beneficial for the delay or treatment of loss of physical function. Data from observational studies and small, uncontrolled intervention studies suggest that physical activity may be beneficial for the treatment of chronic inflammation, but there are no data from a large, long-term, randomized, controlled exercise trial to confirm this potential benefit of exercise training. We propose to conduct an ancillary study to the on-going Lifestyle Interventions and Independence for Elders (LIFE) study, which is a four-site, single-blind randomized, controlled clinical trial in 424 elderly men and women at risk for physical disability. Our primary aim is to measure plasma concentrations of a panel of inflammatory biomarkers in fasting blood samples collected from LIFE participants at baseline, and at 6-mos and 12-mos following randomization to the interventions to test two primary hypotheses that: 1) compared to a non-exercise health education intervention, a 12-month exercise training intervention will decrease con- centrations of inflammatory biomarkers (specifically CRP and IL-6) in elderly men and women at high risk for physical disability, and 2) 12-mo changes in measures of physical function (400m walk time, 4m walking speed, and chair rise time) will be inversely related to changes in the biomarkers. With completion of 180 persons per group, we will have at least 80% power to detect a 36% change in CRP, and a 20% change in IL-6, as a result of the LIFE exercise training intervention. We also propose to conduct statistical analyses to test the following secondary hypotheses: 1) the effects of the exercise intervention on inflammatory biomarkers will be independent of changes in body fat mass in a subset of LIFE participants with measures of body composition, 2) baseline measures of physical function will be related to a summary inflammation status variable derived through factor analysis of the panel of inflammatory biomarkers, and 3) the exercise intervention will reduce this summary inflammatory status variable compared to the no-exercise intervention. The results of this study will provide new knowledge regarding the effects of exercise training on several indicators of chronic inflammation and will yield valuable empirical data about which individual or combina- tion of inflammatory markers are better predictors of poor physical function in the elderly.